The development of novel biodegradable proprietary microspheres containing one or more analgesic and anti-inflammatory peptides that can be released in the joint, over a sustained period of time, is proposed. The overall aim of this drug delivery approach is to effectively manage the chronic pain and inflammation following joint surgery and decrease the longer term problems such as the development of osteoarthritis. Initial studies have demonstrated that microspheres formed by complex coacervation from chondroitin sulfate and gelatin can efficiently encapsulate and release model proteins. Release can be in response to matrix metalloproteases which are elevated in inflamed or diseased joints. The synthesis of microspheres and the encapsulation of peptides and proteins can be controlled by several experimental parameters including crosslinking between the two polymer components. The goal of Phase I is to work on this proprietary drug delivery system to prepare sustained release microspheres containing potent therapeutic peptides from the opioide and interleukin 1- receptor antagonist classes. We will initiall follow the complex coacervation route to prepare microspheres from chondroitin sulfate-gelatin and chondrotin sulfate-chitosan and to evaluate the encapsulation of selected peptides and their release in synovial fluid and chondrocyte secretions. The goal of Phase II will be to determine the efficacy of these systems in vivo and complete the necessary preclinical testing for a Phase I/II clinical trial. PROPOSED COMMERCIAL APPLICATION The need for effective treatments for pain and inflammation is immense. Therefore, there is a large market potential for the proposed drug delivery system. We anticipate generation of a unique set of products that treat both pain and inflammation over an extended period. This provides the opportunity for improving therapeutic outcomes and reducing costs during rehabilitation following surgery.